Implication of peritubular capillary loss and altered expression of vascular endothelial growth factor in IgA nephropathy
Implication of peritubular capillary loss and altered expression of vascular endothelial growth factor in IgA nephropathy
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DOI：
10.1159/000088405
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发表时间：
2006-01-01
影响因子：
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通讯作者：
Kashihara, Naoki
中科院分区：
文献类型：
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作者：
Namikoshi, Tamehachi;Satoh, Minoru;Kashihara, Naoki
背景/目的：为了确定肾小管周围毛细血管（PTC）损失和血管内皮生长因子（VEGF）及其转录因子缺氧诱导因子-1（HIF-1）表达在伊加肾病（IgAN）进展中的作用，我们分析了不同严重程度的IgAN患者中VEGF和HIF-1的表达以及PTC的数量。研究方法：IgAN患者（n = 23）的肾活检标本根据间质损伤评分进行分类：0级（0%）、1级（1-25%）、2级（25-50%）和3级（50-100%）。我们检测了CD 34、VEGF和HIF-1 α的免疫组化表达。结果如下：VEGF在肾小管上皮细胞的胞质中表达，与0级（23.4 +/- 4.5%）相比，1级（35.5 +/-5.9%，平均值+/- SD）和2级（32.5 +/- 5.9%）中VEGF阳性面积显著扩大。2级（559 +/- 49/mm（2））和3级（510 +/- 56/mm（2））的PTC数量显著低于0级（708 +/- 49/mm（2））。HIF-1 α在0级肾小管上皮细胞中弱表达，随着进展到2级而增加，并且在3级中显著降低。1级时囊周间质区也增加。HIF-1 α的表达模式与VEGF的表达模式不平行。在5例肾小球轻微异常的对照患者的肾活检中，VEGF和HIF-1 α的肾小球表达水平与IgAN 0级肾相似。结论：VEGF在IgAN早期产生加速，但对PTC损伤/丢失没有保护作用。VEGF和HIF-1 α表达之间缺乏相关性提示IgAN中VEGF的产生不依赖于HIF。
Background/Aims: To determine the roles of peritubular capillary (PTC) loss and expression of vascular endothelial growth factor ( VEGF) and its transcription factor, hypoxia-inducible factor-1 (HIF-1), in the progression of IgA nephropathy (IgAN), we analyzed the expression of VEGF and HIF-1, and the number of PTCs in patients with variable severity of IgAN. Methods: Renal biopsy specimens from patients with IgAN (n = 23) were classified according to interstitial injury score: grade 0 (0%), grade 1 (1-25%), grade 2 (25-50%) and grade 3 (50-100%). We examined the immunohistochemical expression of CD34, VEGF and HIF-1 alpha. Results: VEGF was expressed in the cytoplasm of tubular epithelia, and VEGF-positive area significantly expanded in grades 1 (35.5 +/- 5.9%, mean +/- SD) and 2 (32.5 +/- 5.9%) compared with grade 0 (23.4 +/- 4.5%). The numbers of PTCs were significantly lower in grades 2 (559 +/- 49/mm(2)) and 3 (510 +/- 56/mm(2)) than grade 0 (708 +/- 49/mm(2)). HIF-1 alpha was weakly expressed in tubular epithelia in grade 0, increased with progression to grade 2, and markedly decreased in grade 3. It was also increased in pericapsular interstitial area in grade 1. The expression pattern of HIF-1 alpha did not parallel that of VEGF. In renal biopsies of 5 control patients with minor glomerular abnormality, glomerular expression levels of VEGF and HIF-1 alpha were similar to those of IgAN grade 0 kidneys. Conclusion: VEGF production was accelerated in the early stage of IgAN but it did not protect against PTC injury/loss. The lack of correlation between VEGF and HIF-1 alpha expression suggests HIF-independent VEGF production in IgAN.